Very low monomethyl fumarate exposure via human milk: a case report-a contribution from the ConcePTION project.

Introduction: While breastfeeding is recommended, knowledge regarding medicine transfer to human milk and its safety for nursing infants is limited. Only one paper has previously described dimethyl fumarate (DMF) transfer during breastfeeding in two patients at 5 and 6 months postpartum, respectively. The current case report describes maternal pharmacokinetic data of monomethyl fumarate (MMF), the active metabolite of DMF, and infant exposure estimations of MMF at 3 months postpartum. Methods: A 32-year-old Caucasian woman started DMF therapy (120 mg, 2x/day) for multiple sclerosis at 3 months postpartum, after weaning her infant from breastfeeding. On day 99 after birth, the patient collected four milk samples over 24 h after 6 days of treatment at the initial dose. Additionally, a single maternal blood sample was collected to calculate the milk-to-plasma (M/P) ratio. The samples were analyzed using liquid chromatography coupled with the mass spectrometry method. Results: A wide range of measured steady-state concentrations of MMF (5.5-83.5 ng/mL) was observed in human milk samples. Estimated daily infant dosage values for MMF, calculated with 150 and 200 mL/kg/day human milk intake, were 5.76 and 7.68 µg/kg/day, and the relative infant doses were 0.16 and 0.22%. The observed mean M/P ratio was 0.059, similar to the M/P ratio predicted using the empirical Koshimichi model (0.06). Discussion: Combining this case report with the two previously described cases, the estimated infant exposure is low, albeit with relevant intra- and inter-patient variabilities. Research should further focus on infant exposure and safety.

Role of breastfeeding in disease prevention.

Human milk provides the infant with many bioactive factors, including immunomodulating components, antimicrobials and prebiotics, which modulate the infant microbiome and immune system maturation. As a result, breastfeeding can impact infant health from infancy, through adolescence, and into adulthood. From protecting the infant from infections, to reducing the risk of obesity, type 1 diabetes and childhood leukaemia, many positive health outcomes are observed in infants receiving breastmilk. For the mother, breastfeeding protects against postpartum bleeding and depression, increases weight loss, and long-term lowers the risk of type 2 diabetes, breast and ovarian cancer, and cardiovascular diseases. Beyond infants and mothers, the wider society is also impacted because of avoidable costs relating to morbidity and mortality derived from a lack of human milk exposure. In this review, Medline was used to search for relevant articles to discuss the health benefits of breastfeeding and its societal impact before exploring future recommendations to enhance our understanding of the mechanisms behind breastfeeding's positive effects and promote breastfeeding on a global scale.

Infant formula supplemented with milk fat globule membrane compared with standard infant formula for the cognitive development of healthy term-born formula-fed infants: protocol for a randomised controlled trial.

INTRODUCTION: Milk fat globule membrane (MFGM) is a complex lipid-protein structure in mammalian milk and human milk that is largely absent from breastmilk substitutes. The objective of this trial is to investigate whether providing infant formula enriched with MFGM versus standard infant formula improves cognitive development at 12 months of age in exclusively formula-fed full-term infants. METHODS AND ANALYSIS: This is a randomised, controlled, clinician-blinded, researcher-blinded and participant-blinded trial of two parallel formula-fed groups and a breastfed reference group that were recruited in the suburban Adelaide (Australia) community by a single study centre (a medical research institute). Healthy, exclusively formula-fed, singleton, term-born infants under 8 weeks of age were randomised to either an MFGM-supplemented formula (intervention) or standard infant formula (control) from enrolment until 12 months of age. The reference group was not provided with formula. The primary outcome is the Cognitive Scale of the Bayley Scales of Infant Development, Fourth Edition (Bayley-IV) at 12 months. Secondary outcomes are the Bayley-IV Cognitive Scale at 24 months, other Bayley-IV domains (language, motor, emotional and behavioural development) at 12 and 24 months of age, infant attention at 4 and 9 months of age, parent-rated language at 12 and 24 months of age, parent-rated development at 6 and 18 months of age as well as growth, tolerance and safety of the study formula. To ensure at least 80% power to detect a 5-point difference in the mean Bayley-IV cognitive score, >200 infants were recruited in each group. ETHICS AND DISSEMINATION: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/19/WCHN/140). Caregivers gave written informed consent prior to enrolling in the trial. Findings of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12620000552987; Australian and New Zealand Clinical Trial Registry: anzctr.org.au.

Antidepressant Medication Use During Lactation: A Review for Providers.

This article presents a summary of information found within the existing medical literature on the pharmacological treatment options for maternal depression during lactation and the concurrent effects on the breastfeeding infant. Existing data on safety and efficacy varies by treatment modality. Medications used to treat depression are all secreted in breast milk to some extent; however, most antidepressants are considered relatively safe to use during breastfeeding. The selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine are present in low levels and are considered preferred agents. Safety data for other antidepressants varies, however. monoamine oxidase inhibitors (MAOIs) should generally be avoided. Available references and resources can help providers optimize treatment of maternal depression while mitigating risk to the infant. Optimizing treatment of maternal depression is a complicated undertaking, which should be made in conjunction with the provider through shared decision making with the patient. Specific properties of any proposed medication, such as the relative infant dose and side effect profile, should always be taken into account during the decision-making process.

Personalized Nutrition with Banked Human Milk for Early Gut Microbiota Development: In Pursuit of the Perfect Match.

The correct initial colonization and establishment of the gut microbiota during the early stages of life is a key step, with long-lasting consequences throughout the entire lifespan of the individual. This process is affected by several perinatal factors; among them, feeding mode is known to have a critical role. Breastfeeding is the optimal nutrition for neonates; however, it is not always possible, especially in cases of prematurity or early pathology. In such cases, most commonly babies are fed with infant formulas in spite of the official nutritional and health international organizations' recommendation on the use of donated human milk through milk banks for these cases. However, donated human milk still does not totally match maternal milk in terms of infant growth and gut microbiota development. The present review summarizes the practices of milk banks and hospitals regarding donated human milk, its safety and quality, and the health outcomes in infants fed with donated human milk. Additionally, we explore different alternatives to customize pasteurized donated human milk with the aim of finding the perfect match between each baby and banked milk for promoting the establishment of a beneficial gut microbiota from the early stages of life.

Post Natal Microbial and Metabolite Transmission: The Path from Mother to Infant.

The entero-mammary pathway is a specialized route that selectively translocates bacteria to the newborn's gut, playing a crucial role in neonatal development. Previous studies report shared bacterial and archaeal taxa between human milk and neonatal intestine. However, the functional implications for neonatal development are not fully understood due to limited evidence. This study aimed to identify and characterize the microbiota and metabolome of human milk, mother, and infant stool samples using high-throughput DNA sequencing and FT-ICR MS methodology at delivery and 4 months post-partum. Twenty-one mothers and twenty-five infants were included in this study. Our results on bacterial composition suggest vertical transmission of bacteria through breastfeeding, with major changes occurring during the first 4 months of life. Metabolite chemical characterization sheds light on the growing complexity of the metabolites. Further data integration and network analysis disclosed the interactions between different bacteria and metabolites in the biological system as well as possible unknown pathways. Our findings suggest a shared bacteriome in breastfed mother-neonate pairs, influenced by maternal lifestyle and delivery conditions, serving as probiotic agents in infants for their healthy development. Also, the presence of food biomarkers in infants suggests their origin from breast milk, implying selective vertical transmission of these features.

A Review: The Effect of Bovine Colostrum on Immunity in People of All Ages.

Bovine colostrum provides newborn calves with strong passive immunity, which will further affect the immunity of their offspring. Compared with other commercial dairy products, bovine colostrum emphasizes the limit of aflatoxin M1, pathogenic bacteria, microorganisms, antibiotics, stimulants, and other items, so it is safe to use. There are many reports that the use of bovine colostrum as a breast milk fortifier for preterm infants provides necessary immune support for premature infants, but the selection of bovine colostrum products chosen must be free of Bacillus cereus because they are very dangerous for premature infants. This also emphasizes that for the bovine colostrum that is used in preterm infants, more clinical research support is needed. At the same time, it should also be emphasized that the composition of BC is different from that of human colostrum, in particular, the main protein of BC is casein, while the main protein in breast milk is whey protein, especially α-lactalbumin, which together with ovalbumin is still the reference protein with the best biological value, especially for muscles. Therefore, bovine colostrum is currently not a complete substitute for breast milk. In recent years, in addition to reports of bovine colostrum use in preterm infants, studies have also found that bovine colostrum has immunomodulatory and promoting effects in adolescents, adults, and the elderly. This suggests that bovine colostrum has the potential to provide appropriate immune support for people of all ages. Therefore, this study aimed to evaluate the quality of nutritional characteristics of bovine colostrum on three dimensions. The effects of bovine colostrum on people of all ages is a narrative review of the effects of bovine colostrum on immunity in people of all ages. This review identified several classes of immunoactive substances in bovine colostrum, including immunoglobulins, cytokines, and enzymes, and compared the nutritional composition of bovine colostrum with mature milk, colostrum and mature milk in full-term breast milk, and colostrum and mature milk in preterm breast milk, to demonstrate that bovine colostrum provides a rich range of immunoactive components. In addition, the influencing factors affecting the quality of bovine colostrum (immunoglobulin) were reviewed, and it was found that individual differences, environmental factors, and processing methods had a great impact on the quality of BC. More importantly, the immunomodulatory effects of bovine colostrum in people of all ages were reviewed in detail (with an emphasis on preterm infants and immunocompromised children in neonates) as evidence to support the immunity effects of colostrum in people of all ages. This review hopes to use the above evidence to make people understand the health role of bovine colostrum as having a human immunomodulatory effect, and at the same time, when seeing the potential value of bovine colostrum in the future, the limitations of its application should also be deeply re-explored, such as lactose intolerance, allergies, etc., to provide effective solutions for the wide application of bovine colostrum.

Human Milk Protein-Derived Bioactive Peptides from In Vitro-Digested Colostrum Exert Antimicrobial Activities against Common Neonatal Pathogens.

Human milk reduces risk for necrotizing enterocolitis in preterm infants. Necrotizing enterocolitis occurs in the ileocecal region where thousands of milk protein-derived peptides have been released from digestion. Digestion-released peptides may exert bioactivity, such as antimicrobial and immunomodulatory activities, in the gut. In this study, we applied mass spectrometry-based peptidomics to characterize peptides present in colostrum before and after in vitro digestion. Sequence-based computational modeling was applied to predict peptides with antimicrobial activity. We identified more peptides in undigested samples, yet the abundances were much higher in the digested samples. Heatmapping demonstrated highly different peptide profiles between undigested and digested samples. Four peptides (αS1-casein [157-163], αS1-casein [157-165], ß-casein [153-159] and plasminogen [591-597]) were selected, synthesized and tested against common pathogenic bacteria associated with necrotizing enterocolitis. All four exhibited bacteriostatic, though not bactericidal, activities against Klebsiella aerogenes, Citrobacter freundii and Serratia marcescens, but not Escherichia coli.

Streptococcus raffinosi sp. nov., isolated from human breast milk samples.

Novel Gram-positive, catalase-negative, α-haemolytic cocci were isolated from breast milk samples of healthy mothers living in Hanoi, Vietnam. The 16S rRNA gene sequences of these strains varied by 0-2 nucleotide polymorphisms. The 16S rRNA gene sequence of one strain, designated as BME SL 6.1T, showed the highest similarity to those of Streptococcus salivarius NCTC 8618T (99.4 %), Streptococcus vestibularis ATCC 49124T (99.4 %), and Streptococcus thermophilus ATCC 19258T (99.3 %) in the salivarius group. Whole genome sequencing was performed on three selected strains. Phylogeny based on 631 core genes clustered the three strains into the salivarius group, and the strains were clearly distinct from the other species in this group. The average nucleotide identity (ANI) value of strain BME SL 6.1T exhibited the highest identity with S. salivarius NCTC 8618T (88.4 %), followed by S. vestibularis ATCC 49124T (88.3 %) and S. thermophilus ATCC 19258T (87.4 %). The ANI and digital DNA-DNA hybridization values between strain BME SL 6.1T and other species were below the cut-off value (95 and 70 %, respectively), indicating that it represents a novel species of the genus Streptococcus. The strains were able to produce α-galactosidase and acid from raffinose and melibiose. Therefore, we propose to assign the strains to a new species of the genus Streptococcus as Streptococcus raffinosi sp. nov. The type strain is BME SL 6.1T (=VTCC 12812T=NBRC 116368T).

Cost analysis of establishing and operating the first human milk bank at Da Nang Hospital for Women and Children in Vietnam: an activity-based costing ingredients study.

BACKGROUND: Breastfeeding is the biological norm for feeding infants and young children. When mothers' breastmilk is unavailable, donor human milk (DHM) from a human milk bank (HMB) becomes the next option for small vulnerable newborns. A comprehensive cost analysis is essential for understanding the investments needed to establish, operate, and scale up HMBs. This study aims to estimate and analyze such costs at the first facility established in Vietnam. METHODS: An activity-based costing ingredients (ABC-I) approach was employed, with the cost perspective from service provision agencies (specifically, the project conducted at Da Nang Hospital for Women and Children and Development Partners). Estimated financial costs, based on actual expenditures, were measured in 2023 local currency and then converted to 2023 US dollars (USD). We examined three scenarios: 1) direct start-up costs + indirect start-up costs + implementation costs, 2) direct start-up costs + implementation costs, and 3) capital costs + implementation costs over the 6.5 years of operation. RESULTS: The total start-up cost was USD 616,263, with total expenditure on direct activities at USD 228,131 and indirect activities at USD 388,132. Investment in equipment accounted for the largest proportion (USD 84,213). The monthly costs of Da Nang HMB were USD 25,217, 14,565, and 9,326, corresponding to scenarios 1, 2, and 3, respectively. Over HMB's 6.5 years of operation, on average, the unit costs were USD 166, USD 96, and USD 62 for DHM received and USD 201, USD 116, and USD 74 for pasteurized DHM meeting specified criteria in the corresponding scenarios. Unit costs were highest in the initial six months, decreased, and reached their lowest levels after a year. Then, the unit costs experienced an increase in late 2020 and early 2021. CONCLUSION: Although the unit cost of DHM in Da Nang HMB is comparable to that in certain neighboring countries, intentional measures to reduce disposal rates, improve HMB efficiency, motivate more community-based donors, and establish an HMB service network should be implemented to lower costs.

Prevalence and concentration of aflatoxin M1 in breast milk in Africa: a meta-analysis and implication for the interface of agriculture and health.

Breast milk is one of the many distinct forms of food that can be contaminated with aflatoxin M1 (AFM1). They may be consumed by eating contaminated foods, such as contaminated meat and crops, which would then be present in breast milk and cause health problems, including nervous system disorders and cancers of the lungs, liver, kidneys, and urinary tract. However, the prevalently inconsistent explanation of prevalence and concentration remains a big challenge. Thus, this meta-analysis was conducted to determine the prevalence and concentration of harmful chemicals in breast milk in an African context. The databases MEDLINE, PubMed, Embase, SCOPUS, Web of Science, and Google Scholar were searched for both published and unpublished research. To conduct the analysis, the collected data were exported to Stata version 18. The results were shown using a forest plot and a prevalence with a 95% confidence interval (CI) using the random-effects model. The Cochrane chi-square (I2) statistics were used to measure the studies' heterogeneity, and Egger's intercept was used to measure publication bias. This review included twenty-eight studies with 4016 breast milk samples and newborns. The analysis showed the overall prevalence and concentration of aflatoxin M1 in breast milk were 53% (95% CI 40, 65; i2 = 98.26%; P = 0.001). The pooled mean aflatoxin M1 concentration in breast milk was 93.02 ng/l. According to this study, the eastern region of Africa was 62% (95% CI 39-82) profoundly affected as compared to other regions of the continent. In subgroup analysis by publication year, the highest level of exposure to aflatoxins (68%; 95% CI 47-85) was observed among studies published from 2010 to 2019. This finding confirmed that more than half of lactating women's breast milk was contaminated with aflatoxin M1 in Africa. The pooled mean aflatoxin M1 concentration in breast milk was 93.02 ng/l. According to this study, the eastern region of Africa was profoundly affected compared with other regions. Thus, the government and all stakeholders must instigate policies that mitigate the toxicity of aflatoxins in lactating women, fetuses, and newborns.

Brasil reúne 26 países em defesa de regulação dos substitutivos do leite materno

Ministério da Saúde brasileiro lidera iniciativa de regulamentar a comercialização digital dos produtos, buscando incorporação internacional. Durante a programação da 77ª Assembleia Mundial da Saúde, o Brasil fez uma declaração conjunta em nome de 27 países, defendendo uma resolução para regulamentar a comercialização digital de substitutivos do leite materno e sua incorporação no Código Internacional. “É poderosa a influência da comercialização de substitutivos do leite materno como uma barreira à amamentação. Estamos enfrentando um desafio emergente”, disse o secretário Carlos Gadelha, representante brasileiro no evento da Organização Mundial da Saúde (OMS).

Dia Mundial da Doação de Leite Humano: campanha busca ampliar recém-nascidos beneficiados no Brasil

Dados consolidados de 2023 mostram que o Ministério da Saúde registrou a doação de 253 mil litros de leite humano a partir da ação de 198 mil mulheres. Com isso, 225,7 mil recém-nascidos foram diretamente beneficiados.

Congresso sobre bancos de leite reúne mais de 200 profissionais em Angola

Mais de 200 profissionais de saúde de 15 diferentes estados de Angola participaram do Congresso de Bancos de Leite Humano da Comunidade dos Países de Língua Portuguesa (CPLP), em Luanda, no país africano. O evento, teve como tema "Segurança alimentar e nutricional para recém-nascidos de risco e lactentes" e foi uma iniciativa conjunta dos governos do Brasil e de Angola, em colaboração com a direção da comunidade.

Ministério da Saúde lança campanha anual de doação de leite humano

Em 2023, o Ministério da Saúde registrou a doação de 253 mil litros de leite humano a partir da ação de 198 mil mulheres. Com isso, 225.762 recém-nascidos foram diretamente beneficiados. O número é 8% maior do que o registrado em 2022 e representa 55% da real necessidade por leite humano no Brasil. Com o objetivo de ampliar ainda mais esse quantitativo, a pasta lançou, nesta segunda-feira (6), a campanha ‘Doe leite materno: vida em cada gota recebida’. A meta para 2024 é ampliar mais 5% a oferta de leite materno a recém-nascidos internados nas unidades neonatais do país.

Impact of Holder Pasteurization and Preanalytical Handling Techniques on Fat Concentration in Donor Human Milk: A Scoping Review.

BACKGROUND: Donor human milk (DHM) is an essential source of nutrition among high-risk infants (e.g., premature and low-birth weight). Holder pasteurization, a common step in DHM processing, is known to partially alter the composition of DHM; however, the impact on fat composition is historically inconsistent. OBJECTIVES: This scoping review aimed to broadly review the literature on the impact of Holder pasteurization on the fat content in DHM, with a focus on preanalytical sample mixing. METHODS: A systematic search of original, peer-reviewed research articles was conducted on 11 July, 2022. Articles were included if they compared matched raw (control) and Holder-pasteurized human milk samples and measured total lipids, cholesterol, and individual classes of fatty acids. Article review and selection was conducted by 2 independent reviewers. RESULTS: The search yielded 26 original, peer-reviewed research articles published between 1978 and 2022. Overall methodology varied considerably between studies. When study methods described any mixing for collecting raw milk, 1 (17%) of the 6 of studies reported a small change in total fat concentration following pasteurization (<5%). Alternatively, among studies that did not describe methods for mixing raw milk to ensure a representative sample, 10 (56%) of the 18 reported a significant change (≥± 5%) in total fat concentration, with changes ranging from -28.6% to +19.4%. CONCLUSIONS: This review suggests that inconsistent findings regarding the impact of Holder pasteurization on fat may be related to study methodologies, particularly preanalytical sample mixing. More research considering the role of preanalytical handling procedures and methodologies is necessary to help clarify the impact of Holder pasteurization on human milk composition.

Efficacy and safety of acupuncture for postpartum hypogalactia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postpartum hypogalactia (PH) is prominent during lactation and may negatively impact the mother's or infant's health. Acupuncture is widely used to increase maternal breast milk production. However, the effects of acupuncture on PH remain unclear. Therefore, this review aimed to evaluate the efficacy and safety of acupuncture in individuals with PH. MATERIALS AND METHODS: Articles on potentially eligible randomized controlled trials (RCTs) on acupuncture for PH published from database inception to October 2023 were retrieved from the PubMed, Web of Science, Cochrane Library, EMBASE, EBSCO, Scopus, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, WanFang, and VIP databases. Two reviewers independently screened the records, extracted essential information, and evaluated the methodological quality of the RCTs using the revised Cochrane risk-of-bias (RoB) tool. The primary outcome was a change in serum prolactin (PRL) levels before and after treatment. Secondary outcomes included milk secretion volume (MSV), total effective rate (TER), mammary fullness degree (MFD), and exclusive breastfeeding rate (EBR). Meta-analyses were performed using RevMan v5.4. Finally, the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. RESULTS: This study included 19 RCTs involving 2,400 participants. The included studies were classified as having an unclear to high RoB. Our findings indicated that, overall, acupuncture showed a significant effect in increasing serum PRL levels (standardized mean differences [SMDs] = 1.09, 95% confidence interval [CI]: 0.50, 1.68), MSV (SMD = 1.69, 95% CI: 0.53, 2.86), TER (relative risk [RR] = 1.25, 95% CI: 1.10, 1.42), and EBR (RR = 2.01, 95% CI: 1.07, 3.78) compared to that in the control group; however, no difference in MFD (SMD = 1.17, 95% CI: -0.09, 2.42) was observed. In the subgroup analysis, acupuncture combined with Chinese herbs or conventional treatment was significantly more effective in increasing serum PRL levels, MSV, and TER than did Chinese herbs or conventional treatment alone. Moreover, acupuncture alone resulted in significantly higher serum PRL levels compared to Chinese herbs; however, this benefit was not observed for TER and MFD. The quality of evidence was critically low. CONCLUSION: Acupuncture may effectively increase milk secretion in women with PH. However, owing to the low quality of evidence, further rigorously designed studies are warranted to confirm our findings.

A comparison of the breast milk microbiota from women diagnosed with gestational diabetes mellitus and women without gestational diabetes mellitus.

BACKGROUND: Human breast milk (HBM) is a contributing factor in modulating the infant's gut microbiota, as it contains bacteria that are directly transferred to the infant during breastfeeding. It has been shown that children of women diagnosed with gestational diabetes mellitus (GDM) have a different gut microbiota compared to children of women without GDM. Our hypothesis is therefore that women with GDM have a different HBM microbiota, which may influence the metabolic function and capacity of the child later in life. The aim of this study was to investigate whether women with GDM have a different breast milk microbiota 1-3 weeks postpartum compared to women without GDM. METHODS: In this case-control study, a total of 45 women were included: 18 women with GDM and 27 women without GDM. A milk sample was collected from each participant 1 to 3 weeks postpartum and the bacterial composition was examined by 16 S rRNA gene sequencing targeting the V4 region. RESULTS: High relative abundances of Streptococcus and Staphylococcus were present in samples from both women with and without GDM. No difference could be seen in either alpha diversity, beta diversity, or specific taxa between groups. CONCLUSION: Our results did not support the existence of a GDM-associated breast milk microbiota at 1-3 weeks postpartum. Further research is needed to fully understand the development of the gut microbiota of infants born to mothers with GDM.